Method for sterilizing a medical device having a hydrophilic coating

ABSTRACT

A method for sterilizing a medical device comprising a hydrophilic coating using radiation said method comprising the steps of bringing the medical device having such coating in contact with an aqueous liquid for wetting the hydrophilic coating, said liquid comprising a solution of a hydrophilic polymer and sterilizing the device by applying a sufficient amount of radiation provides coated devices showing a significantly increased and prolonged water retention and lower friction coefficient when wet.

RELATED APPLICATION

This application is related to application Ser. No. 09/218,305, filedDec. 22, 1998.

FIELD OF THE INVENTION

The present invention relates generally to sterilization of medicaldevices having hydrophilic coatings and more specific to sterilizationusing radiation. Furthermore, the invention relates to a sterilized setcomprising a medical device provided with a hydrophilic coating and aliquid for wetting the hydrophilic coating, a method for protecting thehydrophilic coating of a medical device having such coating duringsterilization using radiation as well as a medical device having ahydrophilic coating said medical device showing, after sterilizationusing radiation, a prolonged water drain off time and reduced frictionforce.

DESCRIPTION OF THE RELATED ART

It is known to coat medical devices, e.g., catheters for introductioninto human cavities such as blood vessels, digestive organs and theurinary system, with a hydrophilic coating, normally as a minimumapplied on that part of the surface which is introduced or comes intocontact with mucous membranes, etc., during introduction of the device.Whereas such coating is not particularly smooth when dry, so that thehandling of the device may become inconvenient, it becomes extremelyslippery when it is swelled with water, preferably immediately beforeintroduction into the human body and thus ensures a substantiallypainless introduction with a minimum of damage on tissue.

U.S. Pat. No. 3,967,728 to Gordon discloses the use of a sterilelubricant for deposition on and lubricating an uncoated catheter beforeuse.

WO 86/06284 (Astra Meditech Aktiebolag) discloses a wetting and storingdevice for a coated catheter in which the coating may be wetted usingwater or water comprising common salt and possibly bactericidalcompounds or other additives.

GB Patent Application No. 2 284 764 (MMG (Europe Ltd.)) discloses theapplication of a lubricious substance such as a water based jelly to thetip of a non-coated catheter prior to insertion into the urethra.

U.S. Pat. No. 3,648,704 (Jackson) discloses a disposable catheterapparatus in which a lubricant may be applied to the tip of the catheterprior to catherisation.

A large number of methods are known for the production of hydrophilicsurface coatings for improving the slipperiness of a catheter or othermedical device.

These methods are most often based on the fact that the substrate to beprovided with a hydrophilic surface coating, in the course of one ormore process stages with intermediary drying and curing, is coated withone or more (mostly two) layers, which are brought to react with oneanother in various ways, e.g. by polymerization initiated byirradiation, by UV light, by graft polymerization, by the formation ofinterpolymeric network structures, or by direct chemical reaction. Knownhydrophilic coatings and processes for the application thereof are e.g.disclosed in Danish Patent No. 159,018, published European PatentApplication Nos. EP 0 389 632, EP 0 379 156, and EP 0 454 293, EuropeanPatent No. EP 0 093 093 B2, British Patent No. 1,600,963, U.S. Pat. Nos.4,119,094, 4,373,009, 4,792,914, 5,041,100 and 5,120,816, and into PCTPublication Nos. WO 90/05162 and WO 91/19756.

According to a method disclosed in U.S. Pat. No. 5,001,009, ahydrophilic surface coating is prepared on a substrate by applying, intwo stages or in one combined stage, on the substrate a primer reactivewith or adhesive to the substrate and then the actual hydrophilicsurface layer which, in this case, comprises polyvinylpyrrolidone [PVP]as the active constituent. By this method, no chemical reaction takesplace between the components of the two layers applied. When the productremains inside the body only for a short period, there may be a riskthat water will be extracted from the hydrophilic surface coating andinto the tissues of the surrounding mucous membranes etc., owing to ahigher osmotic potential of said tissues. At the same time, there is arisk of abrasion of the coating during insertion. As a result of theextraction of water or loss of coating, the hydrophilic surface coatingwill have a tendency to become less slippery and to stick to surroundingtissues, and the removal of the medical device from the body may causepain or damage the tissue. This is especially a problem when carryingout urodynamic examinations via a catheter.

European Patent No. EP 0 217 771 describes a method of forming ahydrophilic coating in order to retain the slipperiness in use for alonger period of time by applying a non-reactive hydrophilic polymersurface layer to a substrate, applying to the non-reactive hydrophilicsurface polymer a solution comprising a solvent and above 2% (weight pervolume) of an osmolality-increasing compound selected from the groupconsisting of mono and disaccharides, sugar alcohols, and non-toxicorganic and inorganic salts, with the proviso that theosmolality-increasing compound is not a trihalogenide such as KI₃(KI/I₂), and evaporating the solvent. EP 0 217 771 discloses that whenwetting the catheters after drying, catheters having a coating of anon-toxic, osmolality increasing compound retaining their slipperinessfor longer times than corresponding untreated surfaces i.e. coatedcatheters dry more slowly. However EP 0 217 771 is silent with respectto storing the coated catheters in the wetting solution and any type ofsterilization or problems in connection herewith.

International patent publication No. WO 94/16747 discloses a hydrophiliccoating with improved retention of water on a surface, especially asurface of a medical device such as a urethra catheter, prepared byapplying to the surface in one or more process steps at least onesolution of components that will combine to form the hydrophiliccoating. During the final step, the surface is coated with an osmolalitypromoting agent which is dissolved or emulgated in the solution or inthe last solution to be applied when forming the hydrophilic coating. WO94/16747 does not disclose cross-linked coatings.

WO 89/09246 discloses solid shaped structures having a surface coatedwith crosslinked hydrophilic polymer, the coating being durable andexhibiting a low coefficient of friction when wet. It is stated that thedegree of crosslinking is critical and is to be controlled by theoperating conditions chosen as too much crosslinking reduces orcompletely eliminates the low friction surface property, and too littlecrosslinking negatively affects the durability of the coating. WO89/09246 does not disclose the presence of a water soluble orosmolality-increasing compound in the coating.

WO 98/19729 discloses catheter packages wherein the catheter is storedin the wetting medium comprising, e.g., an aqueous solution of NaCl, butWO 98/19729 does not mention a wetting solution comprising a hydrophilicpolymer.

All said coatings are developed for instant swelling immediately beforeuse of the medical device on which the coatings are applied.

It has been found, however, that most hydrophilic coatings lose theirwater retention and that the coefficient of friction increase when thecoatings are stored in water for an extended period of time and/orparticulary after sterilisation using irradiation or autoclaving.

Thus, there is still a need for a hydrophilic coating retaining waterretention and low coefficient of friction when the coatings are storedin water for an extended period of time and/or particularly aftersterilisation using irradiation or autoclaving.

SUMMARY OF THE INVENTION

The present invention relates to a method for sterilizing a medicaldevice comprising a hydrophilic coating using radiation.

Furthermore, the invention relates to a sterilized set comprising amedical device provided with a hydrophilic coating and an aqueous liquidfor wetting the hydrophilic coating.

Still further, the invention relates to a method of protecting thehydrophilic coating of a medical device having such coating duringsterilizing using radiation.

The invention further relates to a medical device comprising ahydrophilic coating said medical device showing, after sterilizationusing radiation, a prolonged water drain off time and a reduced frictionforce.

The invention yet further relates to methods for preparing sterilizedcatheters having hydrophilic coatings.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method for sterilizing a medicaldevice comprising a hydrophilic coating using radiation said methodcomprising the steps of bringing the medical device having such coatingin contact with an aqueous liquid for wetting the hydrophilic coating,said liquid comprising a solution of a hydrophilic polymer andsterilizing the device by applying a sufficient amount of radiation.

It has surprisingly been found that the water retention can be increaseddramatically and the coefficient of friction can be kept low by addinghydrophilic polymers for example polyvinylpyrrolidone or copolymerscontaining N-vinylpyrrolidone, poly(meth)acrylic acid or copolymerscontaining (meth)acrylic acid or (meth)acrylic acid esters,polyacrylamides, polyvinylalcohol and copolymers of partially saponifiedvinylacetate copolymers, polyethylenglycol, polyvinylmethylether,polyvinylmethylether-maleic anhydride and copolymers containingmaleic-anhydride or maleic-acidesters or copolymers containingvinylmethyl-ether, or copolymers thereof, or water solublepolysaccharides or derivatives thereof such as carboxymethylcellulose(CMC) or hydroxyethylcellulose or Xanthane or a derivative thereof tothe liquid for wetting a hydrophilic coating and that these compoundsalso protect these properties during exposure to sterilization usingradiation when wetted with such wetting liquid.

Suitable hydrophilic polymers for the wetting agent may be mixtures ofthe preferred species stated above.

Without limiting the invention to any specific hypothesis, it is assumedthat the effect may be ascribed to one or more of following effects:

1. Dissolved hydrophilic polymer chains in the aqueous liquid penetratephysically bound or crosslinked coatings and stabilise them. Thethickness of the coating is increased which contributes to a highercapacity of retaining water.

2. Dissolved hydrophilic polymer chains in the aqueous liquid penetratesphysically bound or crosslinked coatings and prevent furthercrosslinking during irradiation.

3. Dissolved polymers may be chemically bonded to the hydrophiliccoating during irradiation in the aqueous liquid. This gives rise to athicker layer of coating contributing to a higher capacity of retainingwater.

It is preferred that the hydrophilic polymer is a synthetic polymer andespecially that the hydrophilic polymer is at least compatible with andpreferably of the same type as the hydrophilic polymer of the coating.

Also preferred are polysaccharides selected from the group consisting ofcellulose derivatives and xanthans. Although polysaccharides show atendency of break down on sterilisation using radiation, these compoundshave still proven effective in giving a long retention time, a lowfriction. Normally such compounds show a very pronounced thickeningeffect in water and are used in relatively low amounts.

In a preferred embodiment of the invention the cellulose derivative isCMC or a derivative thereof. CMC is suitably used in an amount from0.005 to 3.0%, depending on the molecular weight and degree ofsubstitution of the polymer preferably about 0.5% giving very goodresults. When using xanthan, the amount used is normally in the rangefrom 0.005 to 1%, preferably about 0.15%.

In an especially preferred embodiment of the invention the hydrophilicpolymer is a polyvinyl pyrrolidone (PVP).

The amount of polyvinyl pyrrolidone to be used according to theinvention may vary and depends i.a. on the molecular weight of thespecific PVP. The higher the molecular weight, the higher is thetendency of gelling. Thus, the use of higher amounts of low molecularweight PVP gives an effect similar to the use of lower amounts of ahigher molecular weight PVP. The amount of a PVP of a given molecularweight PVP to be used is easily determined by the skilled in the art byroutine experiments testing the water retention. When using a PVP havinga relatively low molecular weight above 1000 and preferably above 5000,an amount of 6% by weight has proven to be suitable giving a longretention time, a low friction and no problems with gelling.

It is also considered an aspect of the invention, when working withmedical devices having physically bound or cross-linked hydrophiliccoatings, to include a hydrophilic polymer not forming cross-links withthe coating into the coating and to wet or store the medical device inwater or saline.

Saline or another non-toxic osmolality increasing agent is preferablypresent in the physiological range. Thus, saline is preferably presentin an amount of 0.9%

Furthermore, the invention relates to a sterilized set comprising amedical device provided with a hydrophilic coating and an aqueous liquidfor wetting the hydrophilic coating wherein said device is in contactwith the aqueous liquid, wherein said set has been sterilized usingradiation while in contact with said liquid comprising a solution of ahydrophilic polymer.

In another embodiment of the set of the invention the aqueous liquid isplaced in the package also comprising the medical device provided with ahydrophilic coating. Thus, the catheter is permanently wetted by thewetting liquid and thus ready to use. Such a set may be of the kinddisclosed in WO 98/19729.

It has surprisingly been found that using wetting liquids of the kinddisclosed above, it is possible to provide a catheter which ispermanently wetted by the wetting liquid and thus ready to use and whichmay be sterilised by irradiation or autoclaving and which will retainthe water retention capability and thus low coefficient of friction whenthe coatings are stored in water for an extended period of time.

Sterilization using radiation is normally carried out using beta orgamma radiation.

Normally, a loss of water retention capability of coated catheters isobserved, probably due to loss of non-crosslinked and non-bonded polymerchains from the coating during storage in water or by furthercrosslinking of the coating during irradiation in water.

In the first case a collapse of the coating, when the device is removedfrom the water reservoir, will give a low water retention and increaseof the coefficient of friction during use. In the second case furthercrosslinking will decrease the water content in the coating and hence,the coating will show a low water retention and an increased frictioncoefficient.

Still further, the invention relates in a third aspect to a method ofprotecting the hydrophilic coating of a medical device having suchcoating during sterilizing using radiation, characterized in that thecoating is brought into contact with an aqueous solution comprising ahydrophilic polymer and exposed for the radiation while in contact withthe aqueous solution.

In a fourth aspect, the invention relates to a medical device comprisinga hydrophilic coating said medical device showing, after sterilizationusing radiation, a water drain off time >3 minutes and a friction forceof <0.05 N when testing a 10 cm tube having the hydrophilic coatingfixed on a stainless steel plate with two stainless steel rods as shownin ASTM 1894-93 for both physically bonded hydrophilic coatings of thetype disclosed in WO 94/16747 and for chemically cross-linked coatingsof the types disclosed in i.a. WO 98/58988, WO 98/58989, and WO98/58990.

Using the invention it has proven possible to obtain and retain veryhigh water drain off time and low friction forces.

In a fifth aspect, the invention relates to a method of preparing asterilized catheter having a crosslinked two-layer hydrophilic coatingcomprising the steps of

a) preparing a solution of polyvinyl pyrrolidone dissolved in anethanougamma ethanol/gamma solvent mixture,

b) dipping a raw catheter in the solution and letting it dry at ambienttemperature,

c) dipping the resulting catheter in a PVP-solution containing urea andan ethanol/gamma butyrolactone (85/15) solvent mixture,

d) further drying at elevated temperature,

e) cross-linking the polyvinylpyrrolidone by exposing the coatedcatheter to UV-light having a wave length range between 200 and 300 nm.for from ½ to 15 minutes, and

f) sterilizing the coated catheter while wetted with a. solution of PVPby irradiation.

In a sixth aspect, the invention relates to a method of preparing asterilized catheter having a crosslinked hydrophilic coating withunsaturated poly(methyl vinyl ether/maleicanhydride)/hydroxyethylmethacrylate(HEMA) prepolymers comprising thesteps of

a) preparing a solution of poly(methyl vinyl ether/maleic anhydride) inacetone in a reaction vessel equipped with at stirrer, keeping thereaction mixture at room temperature while adding 1-methylimidazole as acatalyst and hydroxyethylmethacrylate dropwise to the stirred polymersolution during a period of 30 minutes,

b) stirring the mixture for from few minutes to 10 hours at roomtemperature,

c) preparing a primer mixture by dissolving a medical grade polyurethaneand the poly(methyl vinyl ether/maleic anhydride)/HEMA unsaturatedprepolymer in a mixture of THF and acetone,

d) coating a raw catheter with a primer by dipping in the resultingsolution in a manner known per se,

e) dipping the resulting catheter in the solution of poly(methyl vinylether/maleic anhydride)/HEMA unsaturated prepolymer in acetone forapplying a top coat,

f) drying the resulting catheter,

g) cross-linking the poly(methyl vinyl ether/maleic anhydride)/HEMAunsaturated prepolymer polyvinylpyrrolidone by exposing the coatedcatheter to 5 M rads from a high energy electron beam source, and

h) sterilizing the coated catheter while wetted with a solution of PVPby irradiation.

In a seventh aspect, the invention relates to a method of preparing asterilized catheter having a cross-linked single layer of hydrophiliccoating comprising the steps of

a) preparing a solution of polyvinyl pyrrolidone dissolved in anethanol/gamma butyrolactone solvent mixture,

b) dipping a raw catheter in the solution and letting it dry at elevatedtemperature,

c) cross-linking the polyvinylpyrrolidone by exposing the coatedcatheter to UV-light having a wave length range between 200 and 300 nm.for from ½ to 15 minutes, and

d) sterilizing the coated catheter while wetted with a. solution of PVPby irradiation.

In accordance with a preferred embodiment of the invention, the wettingliquid comprises an antibacterial agent such as a silver salt, e.g.,silver sulphadiazine, an acceptable iodine source such as povidoneiodine (also called polyvinylpyrrolidone iodine), chlorhexidine saltssuch as the gluconate, acetate, hydrochloride or the like salts orquaternary antibacterial agents such as benzalkonium chloride or otherantiseptics or antibiotics. Antibacterial agents reduces the risk ofinfection, especially when performing urodynamic examinations.

The wetting liquid may according to the invention comprise an osmolalityincreasing agent such as urea, sodium chloride and/or any salt ororganic low molecular weight compound being physiological acceptable andnon-irritating for adjusting the ion strength of the coatingapproximately to the physiological range, the coating preferably beingisotonic in use.

When using urea, the added amount may vary within very broad limits.

The wetting liquid of the invention may also, if desired, compriseplasticizers for the hydrophilic coating such as diethylene glycol,glycerol, phthalates, sorbitol or the like.

Indicators or buffers for pH or antibodies, e.g. monoclonal antibodiesfor specific proteins, may also be enclosed in the wetting liquid of theinvention.

In accordance with a preferred embodiment pharmaceutically activecompounds such as antioxidants or preservatives such as anti microbialagents or antithrombogenic agents may be added to the composition.

Materials and Methods

Polyvinylpyrrolidone: PVP K 90 available from ISP Inc. having amolecular weight 1,300,000 according to ISP.

Polyvinylpyrrolidone: Plasdone K-25 available from ISP Inc. having amolecular weight 34,000 according to ISP.

Poly(methyl vinyl ether/maleic anhydride) is available as the Gantrez ANseries of copolymers from ISP

Ethanol: Absolute Alcohol.

Gamma butyrolactone: Gamma-butyrolactone from International SpecialtyProducts.

UV catalyst: ESACURE KIP 150 from Lamberti SpA

-   -   Darocure® 1173 from Ciba Geigy.        Method for Determination of the Friction

The Standard Test Method for Static and Kinetic Coefficient of Frictionof Plastic Film and Sheeting, ASTM D 1894-93 was modified for testingthe friction coefficient and wear on plastic tubes and catheters.

The tubes or catheters were cut in lengths of 10 cm and fixed on astainless steel plate with two stainless steel rods as shown in ASTM D1894-93. The rods had diameters comparable with the inner diameter ofthe tubes or catheters to keep their shape even when heavy sledges wereplaced upon them.

The friction was determined after wetting after dipping the specimen inwetting liquid for 1 minute. The force for pulling the sledge wasmeasured in Newtons.

Method for Determination of Water Retention

Water retention was determined by subjectively determining the time forthe liquid to drain off after which the coating is dry using a stopwatch.

Experimental Part

EXAMPLE 1 Preparation of a Catheter Having a Crosslinked Two-layerHydrophilic Coating

5 parts of PVP K 90 and 0.05 part of ESACURE KIP 150 were dissolved in94.95 parts of an ethanol/gamma butyrolactone solvent mixture.PVC-catheters were dipped in the solution and dried 1 minute at ambienttemperature and then dipped in a PVP-solution containing 5 parts of PVP,1 part of urea and 94 parts of an ethanol/gamma butyrolactone (85/15)solvent mixture. The catheters were further dried for 30 minutes at 70°C. and exposed to UV-light having a wave length range between 200 and300 nm. for 5 minutes.

Finally, sterilization of the coated catheter was performed while wettedwith a solution of PVP using irradiation.

EXAMPLE 2 Preparation of a Catheter Having a Crosslinked HydrophilicCoating With Unsaturated Poly(methyl Vinyl Ether/maleicAnhydride)/hydroxyethylmethacrylate(HEMA) Prepolymers

20 parts of Gantrez® AN 119 was dissolved in 200 parts of acetone in areaction vessel equipped with at stirrer. The reaction mixture was keptat room temperature. One drop of 1-methylimidazole was added to thesolution as a catalyst. 5 mole % 2-hydroxyethylmethacrylate, based oncontents of maleic anhydride were added dropwise to the stirred polymersolution during a period at 30 min. The mixture was stirred for further2 hours at room temperature.

A 50:50 primer mixture with 5% solids was prepared by dissolving amedical grade polyurethane and the Poly(methyl vinyl ether/maleicanhydride)/HEMA unsaturated prepolymer in a 50:50 mixture of THF andacetone and was coated on PVC catheters as a primer by dipping in amanner known per se.

The catheters were dipped in the solution of poly(methyl vinylether/maleic anhydride)/HEMA unsaturated prepolymer in acetone forapplying a top coat, dried and exposed to 5 M rads from a high energyelectron beam source.

Afterwards, the cross-linked coatings were hydrolyzed and neutralized ina sodium hydrogen carbonate buffer solution for one hour before drying.

Then, sterilization of the coated catheter was carried out while wettedwith a solution of PVP using irradiation.

The friction tested according to the modified ASTM D 1894-93 method asdescribed above showed a friction force of 0.02 when determined inwater.

EXAMPLE 3

A top coat and a primer solution were prepared as in Example b. To thesolutions was added 1% by weight of the solid Darocure® 1173, a UVphoto-initiator obtainable from Ciba Geigy.

PVC catheters were dipped in the primer solution, dried for 30 minutesand dipped in the top coat solution also containing 1% by weight of thesolid of Darocure® 1173 and dried for further 30 minutes. Then, thecoating was cross-linked by exposure to UV light.

The cross-linked coatings were then hydrolyzed and neutralized in asodium hydrogen carbonate buffer solution for one hour before drying.

Then, sterilization of the coated catheter was carried out while wettedwith a. solution of PVP using irradiation.

The friction tested according to the modified ASTM D 1894-93 method asdescribed above showed a friction force of 0.02 when determined inwater.

EXAMPLE 4 Preparation of a Catheter Having a Cross-linked Single LayerHydrophilic Coating According to the Invention

5 parts of PVP K 90 was dissolved in 95 parts of a ethanol/gammabutyrolactone (85/15) solvent mixture. PVC catheters were dipped in thesolution, dried for 30 minutes at 70° C. and exposed to a UV lighthaving a wave length between 200 and 300 nm for 6 minutes.

Then, sterilization of the coated catheter was carried out while wettedwith a. solution of PVP using irradiation.

The catheter was lubricious in wet condition and had a high abrasionresistance.

EXAMPLE 5

Determination of the water retention time in minutes and the frictionforce in N when using the aqueous wetting liquid according to theinvention as compared to the use of saline for wetting the coating.

A cross-linked coating prepared according to Example a, and thefollowing commercial catheters: an EasiCath® catheter, from ColoplastA/S, a LoFric® catheter from Astra AB, a PuriCath® catheter from MaerskMedical, an AquaCath® catheter from EMS, and a Uro-flo Silky catheterfrom Simcare were tested for determination of the water retention timeand the friction. The coated catheters were compared to an uncoated rawcatheter having no hydrophilic coating.

All catheters were stored in a 6% solution of PVP Plasdone K-25 or insaline and sterilized by irradiation, and water reretention of thecoatings and the force of friction were determined as described above.

The results are summarized in the below Table 1: TABLE 1 6% 6% 0.9%Plasdone 0.5% 0.15% 0.9% Plasdone Liquid saline K-25 CMC Xanthane SalineK-25 Coating Water retention (minutes) Friction Force (N) Example a 1-39 9 9 0.06 0.04 EasiCath ® 1-2 7 0.1 0.04 LoFric ® 1-2 5-7 0.05 0.02PuriCath ® 1-2 5 0.32 0.25 AquaCath ® 1-2 3 0.08 0.06 Uro-flo Silky 1-21-2 0.7 0.35 Raw 0 0 0.8 0.8 catheter

EXAMPLE 6

Determination of the water retention time in minutes and the frictionforce in N for the same wetting liquids before and after sterilizationusing radiation.

The friction force and the water retention were determined as statedabove after the catheters had been stored in the stated solutions fortwo days.

The results are stated in the below Tables 2 and 3. TABLE 2 Waterretention (Minutes) Storage for 48 hours Storage for 48 hours withoutsterilization with sterilization Wetting 0.9% NaCl 0.9% NaCl + 0.9% NaCl0.9% NaCl + Liquid Plasdone Plasdone K25 Coating K25 Example a 3 5 1-3 9EasiCath ® 9 5 1-2 7 LoFric ® 9 5 1-2 5-7 PuriCath ® 9 5 1-2 5 Rawcatheter 0 0 0 0

TABLE 3 Friction Force (N) Storage for 48 hours Storage for 48 hourswithout sterilization with sterilization Wetting 0.9% NaCl 0.9% NaCl +0.9% NaCl 0.9% NaCl + Liquid Plasdone Plasdone K25 Coating K25 Example a0.04 0.13 0.06 0.04 EasiCath ® 0.08 0.09 0.1 0.04 LoFric ® 0.07 0.080.05 0.02 PuriCath ® 0.26 0.31 0.32 0.25 Raw catheter 0.8 0.8 0.8 0.8

The results presented in Tables 2 and 3 show that sterilization by betairradiation of the catheters in an isotonic saline solution reduces thewater retention and increases the friction force of the coatings whereassterilization by irradiation of coated catheters stored in a isotonicsaline solution comprising also 6% Plasdone K-25 does not adverselyeffect water retention or friction force of the coatings. This is thecase for the coating prepared according to Example a as well as forcommercial state of the art catheters.

1-13. (canceled)
 14. A medical device comprising a hydrophilic coating,said hydrophilic coating having, after sterilisation using radiation, awater drain off time of greater than 3 minutes and a friction force ofless than 0.05 N, when the water drain off time and the friction forceare measured on a 10 cm tube having the hydrophilic coating of themedical device, said tube being fixed on a stainless steel plate withtwo stainless steel rods and tested under the conditions set forth inASTM 1894-93.
 15. The medical device according to claim 14 wherein themedical device has been sterilised using radiation while the hydrophiliccoating is in contact with an aqueous liquid including a solution of ahydrophilic polymer.
 16. The medical device according to claim 1,wherein said device is a plastic tube or catheter and the water drainoff time and the friction force are measured on 10 cm of said plastictube or catheter.
 17. The medical device according to claim 15, whereinthe hydrophilic polymer is a synthetic polymer.
 18. The medical deviceaccording to claim 17, wherein the hydrophilic polymer is selected fromthe group consisting of polyvinylpyrrolidone or a copolymer containingN-vinylpyrrolidone, poly(meth)acrylic acid or a copolymer containing(meth)acrylic acid or a (meth)acrylic acid ester, a polyacrylamide,polyvinylalcohol and a copolymer of a partially saponified vinylacetatecopolymer, polyethylenglycol, polyvinylmethylether,polyvinylmethylether-maleic anhydride and a copolymer containingmaleic-anhydride or a maleic acid ester or a copolymer containingvinylmethyl-ether.
 19. The medical device as in claim 18 wherein thehydrophilic polymer is polyvinyl pyrrolidone or a copolymer thereof. 20.The medical device according to claim 15 wherein the hydrophilic polymeris a polysaccharide.
 21. The medical device according to claim 20wherein the hydrophilic polymer is a member selected from the groupconsisting of a water soluble polysaccharide, Xanthane and a derivativeof either.
 22. The medical device according to claim 21 wherein thehydrophilic polymer is CMC or a derivative thereof.
 23. The medicaldevice according the claim 15 wherein the aqueous liquid including asolution of a hydrophilic polymer also contains diethylene glycol,glycerol, phthalates or sorbitol.
 24. A sterilized medical devicecomprising a hydrophilic coating, said medical device having beensterilized while the hydrophilic coating is in contact with an aqueousliquid including a solution of a hydrophilic polymer.
 25. The medicaldevice according to claim 24, wherein the hydrophilic polymer is asynthetic polymer.
 26. The medical device according to claim 25, whereinthe hydrophilic polymer is selected from the group consisting ofpolyvinylpyrrolidone or a copolymer containing N-vinylpyrrolidone,poly(meth)acrylic acid or a copolymer containing (meth)acrylic acid or a(meth)acrylic acid ester, a polyacrylamide, polyvinylalcohol and acopolymer of a partially saponified vinylacetate copolymer,polyethylenglycol, polyvinylmethylether, polyvinylmethylether-maleicanhydride and a copolymer containing maleic-anhydride or a maleic acidester or a copolymer containing vinylmethyl-ether.
 27. The medicaldevice as in claim 26 wherein the hydrophilic polymer is polyvinylpyrrolidone or a copolymer thereof.
 28. The medical device according toclaim 24 wherein the hydrophilic polymer is a polysaccharide.
 29. Themedical device according to claim 28 wherein the hydrophilic polymer isa member selected from the group consisting of a water solublepolysaccharide, Xanthane and a derivative of either.
 30. The medicaldevice according to claim 29 wherein the hydrophilic polymer is CMC or aderivative thereof.
 31. The medical device according the claim 24wherein the aqueous liquid including a solution of a hydrophilic polymeralso contains diethylene glycol, glycerol, phthalates or sorbitol.